LungMap Phase II - Building a multidimensional map of developing human lung

LungMap 第二阶段 - 构建人类肺部发育的多维图

• 批准号: 10000199
• 负责人: Jeffrey A Whitsett
• 金额: $ 89.73万
• 依托单位: CINCINNATI CHILDRENS HOSP MED CTR
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-08-23 至 2024-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10000199
• 关键词: 3-Dimensional; Acinus organ component; Affect; Algorithms; Alveolar; Anatomy; Atlases; Bioinformatics; Blood Vessels; Carbon Dioxide; Cell Nucleus; Cell model; Cell physiology; Cells; Child; Chromatin; Code; Communities; Complex; Confocal Microscopy; Congenital Disorders; DNA; Data; Data Analyses; Data Coordinating Center; Data Display; Defect; Development; Digestion; Disease; Distal; Doctor of Medicine; Endothelium; Epigenetic Process; Fibroblasts; Gases; Gene Expression; Genetic Diseases; Genetic Transcription; Genomics; Gland; Goals; Health Services Research; Human; Image; Image Analysis; Immune; Immunofluorescence Immunologic; In Situ; In Situ Hybridization; Individual; Infant; Internet; Intuition; Life; Link; Lobule; Location; Lung; Lung diseases; Maps; Mediating; Molecular; Morphogenesis; Mus; Normal tissue morphology; Nuclear; Nuclear RNA; Online Systems; Ontology; Organ; Oxygen; Pathogenesis; Patients; Perinatal; Phase; Physiological; Positioning Attribute; Premature Infant; Protein Isoforms; Proteins; Proteomics; RNA; RNA Probes; RNA Splicing; RNA analysis; Research; Resolution; Respiratory physiology; Role; Science; Signal Transduction; Site; Structure; Structure of parenchyma of lung; Technology; Tissue Procurements; Tissues; Trachea; Visualization; Work; XCL1 gene; analysis pipeline; bioinformatics pipeline; cell type; central database; confocal imaging; data access; data visualization; design; diverse data; droplet sequencing; epigenomics; experience; genetic signature; high resolution imaging; high throughput technology; human data; human tissue; image processing; image reconstruction; indexing; insight; lung acinus structure; lung development; lung imaging; member; multidimensional data; multiple omics; new technology; organ growth; postnatal; preservation; programs; reconstruction; scaffold; tool; transcriptome sequencing; transcriptomics; two-dimensional; user-friendly; web portal; web services; web site

ABSTRACT Building a Multidimensional Map of Developing Human Lung – Jeffrey A. Whitsett, M.D. PI Our LungMAP2 project seeks to work in a collaborative consortium to develop operational pipelines to study human lung development from the saccular, alveolar stages of morphogenesis at single cell level of resolution. The project will integrate single cell transcriptomic, chromatin accessibility, 2D and 3D high-resolution confocal microscopy, immunofluorescence, multiprobe RNA in situ hybridization studies to create a detailed molecular map of the cells, cell-cell and cell scaffold interactions in their precise anatomic positions in the developing human lung. Our LungMAP2 Center will work in close concert with the Data Coordinating Center (DCC), other LungMAP2 Centers and the Human Tissue Procurement Core (HTPC) to obtain, annotate, preserve and store human tissues using optimal conditions for imaging and omics analyses. Our LungMAP2 project will produce a detailed structural expression atlas of multiple regions, niches in the human lung. We will develop and validate new technologies for tissue clearing, 3D reconstructions of high-resolution images, multi-probe RNA and IF analysis. We will develop new tissue digestion single cell and single nuclear RNA analyses for precise regional niches of the normal developing human lung, tissue from and in infants with rare congenital lung disorders. We will work in a Consortium to develop useful bioinformatic programs, modeling cell-cell, cell matrix interactions to define the signaling and transcriptional programs building and maintaining organ structure and function. Working with the DCC and other LungMAP2 Centers, our bioinformatics pipelines will enable data visualization, interrogation in user friendly web portals for sharing with members of the LungMAP2 Consortium, the DCC and for the research community in general.

摘要 构建人类肺发育的多维图。医学博士惠特塞特Pi 我们的LungMAP 2项目寻求与合作联盟合作，开发运营管道， 在单细胞水平上从形态发生的囊状、肺泡阶段研究人肺发育 的决议。该项目将整合单细胞转录组学，染色质可及性，2D和3D 高分辨率共聚焦显微镜、免疫荧光、多探针RNA原位杂交研究 以精确的方式创建细胞、细胞-细胞和细胞支架相互作用的详细分子图， 在发育中的人类肺部的解剖位置。我们的LungMAP 2中心将与 数据协调中心（DCC）、其他LungMAP 2中心和人体组织采购 核心（HTPC），以获得，注释，保存和储存人体组织使用的最佳条件， 成像和组学分析。我们的LungMAP 2项目将产生一个详细的结构表达图谱， 多个区域，人体肺部的小生境。我们将开发和验证新的组织技术， 透明化、高分辨率图像的3D重建、多探针RNA和IF分析。我们将 开发新的组织消化单细胞和单核RNA分析，用于精确的区域小生境 正常发育的人类肺组织，来自患有罕见先天性肺病的婴儿的组织。 我们将在一个联盟中开发有用的生物信息学程序，建模细胞-细胞，细胞基质， 相互作用来定义信号和转录程序， 结构和功能。与DCC和其他LungMAP 2中心合作，我们的生物信息学 管道将实现数据可视化，在用户友好的门户网站上进行询问， LungMAP 2联盟、DCC和整个研究界的成员。